RESUMO
Using a specific antibody, we found that expression of the viral restriction factor IFITM3 differs across cell types within the immune compartment with higher expression in myeloid rather than lymphoid cells. IFITM3 expression was increased following IFN stimulation, mostly type I, in immune cells, with the exception of T cells.
Assuntos
Antivirais/metabolismo , Interferon Tipo I/metabolismo , Proteínas de Membrana/metabolismo , Proteínas de Ligação a RNA/metabolismo , Células A549 , Linfócitos T CD4-Positivos/metabolismo , Linhagem Celular , Linhagem Celular Tumoral , Células HEK293 , Humanos , Linfócitos/metabolismoRESUMO
Prostate cancer is a significant global health issue, and limitations to current patient management pathways often result in overtreatment or undertreatment. New ways to stratify patients are urgently needed. We conducted a feasibility study of such novel assessments, looking for associations between genomic changes and lymphocyte infiltration. An innovative workflow using an in-house targeted sequencing panel, immune cell profiling using an image analysis pipeline, RNA sequencing, and exome sequencing in select cases was tested. Gene fusions were profiled by RNA sequencing in 27 of 27 cases, and a significantly higher tumor-infiltrating lymphocyte (TIL) count was noted in tumors without a TMPRSS2:ERG fusion compared with those with the fusion (P = 0.01). Although this finding was not replicated in a larger validation set (n = 436) of The Cancer Genome Atlas images, there was a trend in the same direction. Differential expression analysis of TIL-high and TIL-low tumors revealed the enrichment of both innate and adaptive immune response pathways. Mutations in mismatch repair genes (MLH1 and MSH6 mutations in 1 of 27 cases) were identified. We describe a potential immune escape mechanism in TMPRSS2:ERG fusion-positive tumors. Detailed profiling, as shown herein, can provide novel insights into tumor biology. Likely differences with findings with other cohorts are related to methods used to define region of interest, but this warrants further study in a larger cohort.
Assuntos
Biomarcadores Tumorais , Proteínas de Fusão Oncogênica/genética , Neoplasias da Próstata/genética , Serina Endopeptidases/genética , Classe Ia de Fosfatidilinositol 3-Quinase/genética , DNA Helicases/genética , Reparo de Erro de Pareamento de DNA , Proteínas de Ligação a DNA/genética , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Mutação INDEL , Imuno-Histoquímica , Linfócitos/imunologia , Linfócitos/metabolismo , Linfócitos/patologia , Masculino , Polimorfismo de Nucleotídeo Único , Neoplasias da Próstata/imunologia , Neoplasias da Próstata/patologia , Análise de Sequência de RNA , Regulador Transcricional ERG/genéticaRESUMO
Enrichment of CD103+ tumor-infiltrating T lymphocytes (TIL) is associated with improved outcomes in patients. However, the characteristics of human CD103+ cytotoxic CD8+ T cells (CTL) and their role in tumor control remain unclear. We investigated the features and antitumor mechanisms of CD103+ CTLs by assessing T-cell receptor (TCR)-matched CD103+ and CD103- cancer-specific CTL immunity in vitro and its immunophenotype ex vivo Interestingly, we found that differentiated CD103+ cancer-specific CTLs expressed the active form of TGFß1 to continually self-regulate CD103 expression, without relying on external TGFß1-producing cells. The presence of CD103 on CTLs improved TCR antigen sensitivity, which enabled faster cancer recognition and rapid antitumor cytotoxicity. These CD103+ CTLs had elevated energetic potential and faster migration capacity. However, they had increased inhibitory receptor coexpression and elevated T-cell apoptosis following prolonged cancer exposure. Our data provide fundamental insights into the properties of matured human CD103+ cancer-specific CTLs, which could have important implications for future designs of tissue-localized cancer immunotherapy strategies.
Assuntos
Antígenos CD/metabolismo , Linfócitos T CD8-Positivos/imunologia , Cadeias alfa de Integrinas/metabolismo , Neoplasias Pulmonares/imunologia , Linfócitos do Interstício Tumoral/imunologia , Neoplasias/imunologia , Linfócitos T Citotóxicos/imunologia , Antígenos CD/imunologia , Humanos , Imunofenotipagem/métodos , Cadeias alfa de Integrinas/imunologia , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Neoplasias/metabolismo , Neoplasias/patologia , Prognóstico , Receptores de Antígenos de Linfócitos T/genética , Receptores de Antígenos de Linfócitos T/imunologia , Fator de Crescimento Transformador beta1/imunologia , Fator de Crescimento Transformador beta1/metabolismoRESUMO
OBJECTIVE: To present the diagnosis course and sequelae of a case of anti-N-methyl-D-aspartate (NMDA) receptor encephalitis, drawing attention to early psychiatric symptoms. METHOD: The literature on anti-NMDA encephalitis is reviewed and possible psychopathological mechanisms discussed. RESULT: New onset psychoses, presenting with the combination of hallucinations, dyskinesias and seizures and progressing to catatonia should be referred to neurology for consideration of anti-NMDA receptor encephalitis. CONCLUSION: Early diagnosis is important for a favourable prognosis.